Aldehyde dehydrogenase 2 (ALDH2) is an enzyme that detoxifies endogenous or exogenous aldehydes harmful to a living body, such as acetaldehyde and 4-hydroxynonenal, by oxidizing them.
Thus, ALDH2-activating compounds are expected to have various pharmaceutical effects as listed in Patent Literature 1. Among the ALDH2-activating compounds, N-[(2H-1,3-benzodioxol-5-yl)methyl]-2,6-dichlorobenzamide (hereinafter referred to as “Alda-1”) described in Patent Literature 2 has been reported to have various pharmaceutical effects in the non-clinical studies (for example, Non Patent Literature 1 and Non Patent Literature 2).
However, Alda-1 has challenging problems for its clinical development. Hie problems include production of reactive metabolites. Reactive metabolites are generally known to potentially cause serious blood toxicity and liver damage (Non Patent Literature 3). Clozapine, which is an antipsychotic agent and is an example of drugs causing serious blood toxicity and liver damage, has been reported to produce reactive metabolites abundantly m in vitro tests using matrix from human liver (Non Patent Literatures 4, 5). As demonstrated in Test Example 2 below, Alda-1 is a compound that produces reactive metabolites as much as clozapine.
Therefore, a compound that has an effect of activating ALDH2 and produces a smaller amount of reactive metabolites is desirable.